Medical device for delivering a therapeutic substance and method therefor

ABSTRACT

A device useful for localized delivery of a therapeutic material is provided. The device includes a structure including a porous material; and a water-insoluble salt of a therapeutic material dispersed in the porous material. The water-insoluble salt is formed by contacting an aqueous solution of a therapeutic salt with a heavy metal water-soluble salt dispersed throughout a substantial portion of the porous material. The heavy metal water-soluble salt can be dispersed in the porous material so that the device can be sterilized and the therapeutic material can be loaded in the device in situ, for example, just prior to use. The therapeutic material is preferably a heparin or heparin derivative or analog which renders the material antithrombotic as an implantable or invasive device.

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application is a continuation of U.S. application Ser. No.09/769,423, filed Jan. 26, 2001, which is a continuation of U.S.application Ser. No. 08/877,532, filed Jun. 17, 1997, that issued asU.S. Pat. No. 6,203,536, the disclosures of each of which are herebyincorporated by reference herein in their entireties.

BACKGROUND OF THE INVENTION

[0002] This invention relates to a medical device employing atherapeutic substance as a component thereof. For example in an arterialsite treated with percutaneous transluminal coronary angioplasty therapyfor obstructive coronary artery disease a therapeutic antithrombogenicsubstance such as heparin may be included with a device and deliveredlocally in the coronary artery. Also provided is a method for making amedical device capable of localized application of therapeuticsubstances.

[0003] Medical devices which serve as substitute blood vessels,synthetic and intraocular lenses, electrodes, catheters and the like inand on the body or as extracorporeal devices intended to be connected tothe body to assist in surgery or dialysis are well known. For example,intravascular procedures can bring medical devices into contact with thepatient's vasculature. In treating a narrowing or constriction of a ductor canal percutaneous transluminal coronary angioplasty (PTCA) is oftenused with the insertion and inflation of a balloon catheter into astenotic vessel. Other intravascular invasive therapies includeatherectomy (mechanical systems to remove plaque residing inside anartery), laser ablative therapy and the like. However, this use ofmechanical repairs can have adverse consequences for the patient. Forexample, restenosis at the site of a prior invasive coronary arterydisease therapy occurs in a majority of cases. Restenosis, definedangiograhpically, is the recurrence of a 50% or greater narrowing of aluminal diameter at the site of a prior coronary artery disease therapy,such as a balloon dilatation in the case of PTCA therapy. In particular,an intra-luminal component of restenosis develops near the end of thehealing process initiated by vascular injury, which then contributes tothe narrowing of the luminal diameter. This phenomenon is sometimesreferred to as “intimal hyperplasia.” It is believed that a variety ofbiologic factors are involved in restenosis, such as the extent of theinjury, platelets, inflammatory cells, growth factors, cytokines,endothelial cells, smooth muscle cells, and extracellular matrixproduction, to name a few.

[0004] Attempts to inhibit or diminish restenosis often includeadditional interventions such as the use of intravascular stents and theintravascular administration of pharmacological therapeutic agents.Examples of stents which have been successfully applied over a PTCAballoon and radially expanded at the same time as the balloon expansionof an affected artery include the stents disclosed in U.S. Pat. No.4,733,665 issued to Palmaz, U.S. Pat.No. 4,800,882 issued to Gianturcoand U.S. Pat. No. 4,886,062 issued to Wiktor. Also, such stentsemploying therapeutic substances such as glucocorticoids (e.g.dexamethasone, betamethasone), heparin, hirudin, tocopherol,angiopeptin, aspirin, ACE inhibitors, growth factors, oligonucleotides,and, more generally, antiplatelet agents, anticoagulant agents,antimitotic agents, antioxidants, antimetabolite agents, andanti-inflammatory agents have been considered for their potential tosolve the problem of restenosis.

[0005] Another concern with intravascular and extracorporeal proceduresis the contact of biomaterials with blood which can trigger the body'shemostatic process. The hemostatic process is normally initiated as thebody's response to injury. When a vessel wall is injured, plateletsadhere to damaged endothelium or exposed subendothelium. Followingadhesion of the platelets, these cells cohere to each other preparatoryto aggregation and secretion of their intracellular contents.Simultaneously there is activation, probably by electrostatic charge ofthe contact factors, of the coagulation cascade. The sequentialstep-wise interaction of these procoagulant proteins results in thetransformation of soluble glycoproteins into insoluble polymers, whichafter transamidation results in the irreversible solid thrombus.

[0006] Immobilization of polysaccharides such as heparin to biomaterialshas been used to improve bio- and hemocompatibility of implantable andextracorporeal devices. The mechanism responsible for reducedthrombogenicity of heparinized materials is believed to reside in theability of heparin to speed up the inactivation of serine proteases(blood coagulation enzymes) by AT-Ill. In the process, AT-III forms acomplex with a well defined pentasaccharide sequence in heparin,undergoing a conformational change and thus enhancing the ability ofAT-III to form a covalent bond with the active sites of serine proteasessuch as thrombin. The formed TAT-complex then releases from thepolysaccharide, leaving the heparin molecule behind for a second roundof inactivation.

[0007] Usually, immobilization of heparin to a biomaterial surfaceconsists of activating the material in such away that coupling betweenthe biomaterial and finctional groups on the heparin (—COOH, —OH, —NH₂)can be achieved. For example, Larm presented (in U.S. Pat. No.4,613,665) a method to activate heparin via a controlled nitrous aciddegradation step, resulting in degraded heparin molecules of which apart contains a free terminal aldehyde group. Heparin in this form canbe covalently bound to an aminated surface in a reductive animationprocess. Although the molecule is degraded and as a result shows lesscatalytic activity in solution, the end point attachment of this type ofheparin to a surface results in true anti-thromogenicity due to theproper presentation of the biomolecule to the surface. In this fashion,the molecule is freely interacting with AT-III and the coagulationenzymes, preventing the generation of thrombi and microemboli.

[0008] However, the attachment and delivery of therapeutic substancessuch as heparin can involve complicated and expensive chemistry. It istherefore an object of the present invention to provide a medical devicehaving a biocompatible, blood-contacting surface with an activetherapeutic substance at the surface and a simple, inexpensive methodfor producing such a surface.

SUMMARY OF THE INVENTION

[0009] This invention relates to a medical device having ablood-contacting surface with a therapeutic substance thereon.Preferably, the device according to the invention is capable of applyinga highly localized therapeutic material into a body lumen to treat orprevent injury. The term “injury” means a trauma, that may be incidentalto surgery or other treatment methods including deployment of a stent,or a biologic disease, such as an immune response or cell proliferationcaused by the administration of growth factors. In addition, the methodsof the invention may be performed in anticipation of “injury” as aprophylactic. A prophylactic treatment is one that is provided inadvance of any symptom of injury in order to prevent injury, preventprogression of injury or attenuate any subsequent onset of a symptom ofsuch injury.

[0010] In accordance with the invention, a device for delivery oflocalized therapeutic material includes a structure including a porousmaterial and a plurality of discrete particles of a water-insoluble saltof the therapeutic material dispersed throughout a substantial portionof the porous material. Preferably, the device is capable of beingimplanted in a body so that the localized therapeutic agent can bedelivered in vivo, typically at a site of vascular injury or trauma.More preferably, the porous material is also biocompatible, sufficientlytear resistant and nonthrombogenic.

[0011] The porous material may be a film on at least a portion of thestructure or the porous material may be an integral portion of thestructure. Preferably, the porous material is selected from the group ofa natural hydrogel, a synthetic hydrogel, teflon, silicone,polyurethane, polysulfone, cellulose, polyethylene, polypropylene,polyamide, polyester, polytetrafluoroethylene, and a combination of twoor more of these materials. Examples of natural hydrogels includefibrin, collagen, elastin, and the like.

[0012] The therapeutic agent preferably includes an antithromboticmaterial. More preferably, the antithrombotic material is a heparin orheparin derivative or analog. Also preferably, the insoluble salt of thetherapeutic material is one of the silver, barium or calcium salts ofthe material.

[0013] The structure of the device can be adapted for its intendedextracorporeal or intravascular purpose in an internal human body site,such as an artery, vein, urethra, other body lumens, cavities, and thelike or in an extracorporeal blood pump, blood filter, blood oxygenatoror tubing. In one aspect of the invention, the shape is preferablygenerally cylindrical, and more preferably, the shape is that of acatheter, a stent, or a guide wire.

[0014] In another aspect of the invention, an implantable device capableof delivery of a therapeutic material includes a structure comprising aporous material; and a plurality of discrete particles comprising aheavy metal water soluble salt dispersed throughout a substantialportion of the porous material. Preferably, the heavy metalwater-soluble salt is selected from the group of AgNO₃, Ba(NO₃)₂, BaCl₂,and CaCl₂. The amount of water-soluble salt dispersed throughout aportion of the porous material determines the total amount oftherapeutic material that can be delivered once the device is implanted.

[0015] The invention also provides methods for making an implantabledevice which includes therapeutic materials. In one embodiment, a methodof the invention includes loading a structure comprising a porousmaterial with a heavy metal water-soluble salt dispersed throughout asubstantial portion of the porous material, sterilizing the loadedstructure, and packaging for storage and, optionally, delivery of thesterilized loaded structure. Preferably, the method of the inventionfurther includes substantially contemporaneously loading of awater-soluble therapeutic material, wherein a water insoluble salt ofthe therapeutic material is produced throughout a substantial portion ofthe porous material of the structure. “Substantially contemporaneously,”means that the step of loading a water soluble therapeutic materialoccurs at or near a step of positioning the device proximate to adesired area, i.e., at or near the surgical arena prior toadministration to or implantation in, a patient. More preferably, thewater insoluble salt of the therapeutic material is dispersed throughouta substantial portion of the porous material.

[0016] In another aspect of the invention, a method includes loading astructure comprising a porous material with a heavy metal water-solublesalt dispersed throughout a substantial portion of the porous material;loading a water soluble therapeutic material, wherein a water insolublesalt of the therapeutic material is produced in a substantial portion ofthe porous material of the structure; and packaging for delivery of theloaded structure.

[0017] Thus, the methods for making an implantable device to deliver atherapeutic material and device in vivo, or in an extracorporeal circuitin accordance with the invention, are versatile. A therapeutic materialmay be loaded onto a structure including a porous material at any numberof points between, and including, the point of manufacture and the pointof use. As a result of one method, the device can be stored andtransported prior to incorporation of the therapeutic material. Thus,the end user can select the therapeutic material to be used from a widerrange of therapeutic agents.

BRIEF DESCRIPTION OF THE DRAWINGS

[0018]FIG. 1 is an elevational view of one embodiment of a deviceaccording to the invention with a balloon catheter as a mode of deliveryof the device;

[0019]FIG. 2 is an elevational view of another embodiment of a deviceaccording to the invention with a balloon catheter as a mode of deliveryof the device; and

[0020]FIG. 3 is a flow diagram schematically illustrating methodsaccording to the invention.

[0021]FIG. 4 is a photograph taken from a scanning electron microscopeof a surface showing the insoluble therapeutic material according to theinvention.

[0022]FIGS. 5a and 5 b are photographs showing the histologicalcomparison between a stent heparinized according to the presentinvention (5 a) and a control stent (5 b).

DESCRIPTION OF PREFERRED EMBODIMENTS

[0023] One of the more preferred configurations for a device accordingto the invention is a stent for use in artery/vascular therapies. Theterm “stent” refers to any device capable of being delivered by acatheter and which, when placed into contact with a portion of a wall ofa lumen to be treated, will also deliver localized therapeutic materialat a luminal or blood-contacting portion of the device. A stenttypically includes a lumen wall-contacting surface and a lumen-exposedsurface. Where the stent is shaped generally cylindrical or tube-like,including a discontinuous tube or ring-like structure, the lumen-wallcontacting surface is the surface in close proximity to the lumen wallwhereas the lumen exposed surface is the inner surface of thecylindrical stent. The stent can include polymeric or metallic elements,or combinations thereof, onto which a porous material is applied. Forexample, a deformable metal wire stent is useful as a stent framework ofthis invention, such as that described in U.S. Pat. No. 4,886,062 toWiktor, which discloses preferred methods for making a wire stent. Othermetallic stents useful in this invention include those of U.S. Pat. No.4,733,655 to Palmaz and U.S. Pat. No. 4,800,882 to Gianturco.

[0024] Referring now to FIG. 1, the stent 20 comprises a stent framework22 and a porous material coating 24. The stent framework 22 isdeformable and can be formed from a polymeric material, a metal or acombination thereof. A balloon 16 is positioned in FIG. 1 adjacent thelumen-exposed surface of the stent to facilitate delivery of the stent.The stent 20 can be modified to increase or to decrease the number ofwires provided per centimeter in the stent framework 22. Similarly, thenumber of wire turns per centimeter can also be modified to produce astiffer or a more flexible stent framework.

[0025] Polymeric stents can also be used in this invention. The polymerscan be nonbioabsorbable or bioabsorbable in part, or total. Stents ofthis invention can be completely nonbioabsorbable, totally bioabsorbableor a composite of bioabsorbable polymer and nonabsorbable metal orpolymer. For example, another stent suitable for this invention includesthe self-expanding stent of resilient polymeric material as disclosed inInternational Publication No. WO 91/12779.

[0026] Nonbioabsorbable polymers can be used as alternatives to metallicstents. The stents of this invention should not substantially induceinflammatory and neointimal responses. Examples of biostablenonabsorbable polymers that have been used for stent construction withor without metallic elements include polyethylene terephthalate (PET),polyurethane urea and silicone (for example, see van Beusekom et al.Circulation 86(supp. 1):I-731, 1992 and Lincoff et al. J Am. CallCardial. 21(supp. 1):335A, 1994. Although the porous material is shownas a coating 24, it is to be understood that, for the purposes of thisinvention, the porous material can be incorporated into the material ofthe stent.

[0027] Referring to FIG. 2, an alternative stent 30 is shown. The stentframework 34 is affixed with a film of a porous material 32. This can beaccomplished by wrapping the film 32 around the stent framework 34 andsecuring the film 32 to the framework 34 (i.e., the film is usuallysufficiently tacky to adhere itself to the framework but a medical gradeadhesive could also be used if needed) so that the film 32 will stay onthe balloon 36 and framework 34 until it is delivered to the site oftreatment. The film 32 is preferably wrapped over the framework withfolds or wrinkles that will allow the stent 30 to be readily expandedinto contact with the wall of the lumen to be treated. Preferably, thefilm 32 is located on a lumen-wall contacting surface 33 of the stentframework 34 such that radiation is substantially locally delivered to alumen wall, for example, an arterial wall membrane (not shown).

[0028] Porous Material

[0029] As mentioned above, the device according to the invention isgenerally a structure including a porous material. In one embodiment,the porous material is a film on at least a portion of the structure. Inanother embodiment, the porous material is an integral portion of thestructure. Preferably, the porous material is biocompatible, andsufficiently tear-resistant and nonthrombogenic. More preferably, theporous material is selected from the group of a natural hydrogel, asynthetic hydrogel, teflon, silicone, polyurethane, polysulfone,cellulose, polyethylene, polypropylene, polyamide, polyester,polytetrafluoroethylene, and a combination of two or more of thesematerials. Examples of natural hydrogels include fibrin, collagen,elastin, and the like. In materials which do not include pores in theirusual structural configurations, pores between one micrometer indiameter or as large as 1000 micrometers in diameter can be introducedby conventional means such as by introducing a solvent solubleparticulate material into the desired structure and dissolving theparticulate material with a solvent. However, no particular pore size iscritical to this invention.

[0030] Therapeutic Material

[0031] The therapeutic material used in the present invention could bevirtually any therapeutic substance which possesses desirabletherapeutic characteristics and which can be provided in both watersoluble and water insoluble salts and which have bioactivity as aninsoluble salt. For example, antithrombotics, antiplatelet agents,antimitotic agents, antioxidants, antimetabolite agents,anti-inflammatory agents and radioisotopes could be used. “Insolublesalt” or “water insoluble salt” of the therapeutic substance as setforth herein, means that the salt formed has a relatively poorsolubility in water such that it will not readily disperse from thepores of the device. In particular, anticoagulant agents such asheparin, heparin derivatives and heparin analogs could be used toprevent the formation of blood clots on the device. Also,water-insoluble radioactive salts such as AgI¹²⁵, BaS³⁵O₄,and(Ca)₃(p³²O₄)₂ could be used for application of radiotherapy to a bodylumen or blood.

[0032] Preferably, the water-insoluble salt of the therapeutic materialis formed by a heavy metal water-soluble salt interacting with anaqueous radioactive salt solution. In the present invention, the heavymetal water-soluble salt is dispersed throughout a substantial portionof the porous material. Preferably, the heavy metal water-soluble saltis selected from the group of AgNO₃, Ba(NO₃)₂, BaCl₂, CaCI₂, and amixture thereof. The amount of water-soluble salt dispersed throughout aportion of the porous material determines the ultimate amount oftherapeutic material capable of being administered once the device isimplanted.

[0033] Methods of Making an Implantable Device

[0034] Referring now to FIG. 3, a structure having a porous material isloaded with a heavy metal water-soluble salt. Preferably, this stepincludes contacting, more preferably immersing, the structure with anaqueous solution of the heavy metal water-soluble salt, as describedabove. Preferably, the heavy metal water-soluble salt is dispersedthroughout a substantial portion of the porous material. This may beassisted by degassing the pores of the structure by such techniques asultrasound or vacuum degassing. The resulting structure can now besterilized, packaged and, optionally, stored until use.

[0035] In one embodiment of the invention, a sterilized structure isshipped or delivered to the relevant consumer. The structure issubstantially contemporaneously loaded with a water soluble therapeuticmaterial. Preferably, the loading of the therapeutic material includescontacting, more preferably immersing, the porous material in an aqueoussolution comprising a salt of the therapeutic material, as describedabove. Again, degassing of the device can help to bring the therapeuticmaterial into the pores. A water-insoluble therapeutic salt is therebyformed within the porous material. Examples of aqueous radioactive saltsolutions for radiotherapy include Nal¹²⁵ K₂S³⁵O₄, NaS³⁵O₄, an Na₃P³²O₄,to name a few.

[0036] This method is advantageous in that the structure can be loadedwith the therapeutic material in situ, i.e., at or near the point oftherapeutic use, typically before administration, preferablyimplantation, to a patient. This is particularly useful because thedevice can be stored and transported prior to incorporation of thetherapeutic material. This feature has several advantages. For example,the relevant consumer can select the therapeutic material to be usedfrom a wider range of therapeutic materials, e.g., a radioisotope with acertain half-life with certain particle emitting characteristics can beselected. Thus, the therapeutic material selected is not limited to onlythose supplied with the device but can instead be applied according tothe therapy required.

[0037] In another aspect of the invention, a sterilized structure isloaded with a therapeutic material. Preferably, the loading of thetherapeutic material includes contacting, more preferably immersing, theporous material in an aqueous solution comprising a salt of thetherapeutic material, wherein a water-insoluble salt of the therapeuticmaterial is formed within the porous material. Examples of therapeuticsalt solutions may be those previously mentioned above. The structure ispreferably packaged and can shipped to the relevant consumer. Thestructure can now be administered, preferably implanted, to a patient.Thus, in this embodiment, the structure is loaded with the therapeuticmaterial prior to reaching the point of use, which may be moreconvenient depending upon the facilities available to the relevantconsumer.

[0038] The following non-limiting examples will further illustrate theinvention. All parts, percentages, ratios, etc. are by weight unlessotherwise indicated.

EXAMPLE 1

[0039] The following solutions were used in the procedure:

[0040] Solution A: 1-10% aqueous solution of BaCl₂

[0041] Solution B: 1-10% aqueous solution of Ba(NO₃)₂

[0042] Solution C: 1-10% aqueous solution of Na₂S³⁵O₄

[0043] A gamma-radiation sterilized porcine fibrin stent made accordingto U.S. Pat. No. 5,510,077 was treated by rehydration in Solution A byimmersion for about 5 to about 10 minutes, the stent was removed andexcess solution was blotted with absorbent paper. The stent was thendehydrated and sterilized by gamma radiation.

[0044] This treated stent was then rehydrated in an aqueous solution ofNa₂S³⁵O₄ radioisotope having a specific activity of about 10 μCi/ml toabout 500 μCi/ml. A white precipitate of BaS³⁵O₄ was observed within thepores of the stent surface. The stent can now be implanted into anartery for localized delivery of β-radiation or packaged for delivery tothe consumer.

EXAMPLE 2

[0045] Fibrin stents made according to U.S. Pat. No. 5,510,077 weresoaked in a 20% by weight solution of BaCl₂ (preferably soaking forabout 10 to 30 minutes). The stents were then subjected to degassing byvacuum to remove air from the pores of the fibrin matrix, thus allowingthe BaCl₂ solution to fill the pores. The stents were dried overnight.The dried stents were placed into a solution of sodium heparinate(preferably soaking in a solution of 1000 U/ml to 20,000 U/ml for 10-20minutes—most preferably a solution of at least 10,000 U/ml) to allow theBaCl₂ in the fibrin matrix to react with the sodium heparinate to formbarium heparinate which was precipitated within the fibrin matrix.Scanning electron microscopy (SEM) showed that particulates of bariumheparinate in the order of 10 microns and smaller were trapped withinthe fibrin matrix (FIG. 4). In vivo evaluation of the barium heparinatestents were carried out using a carotid crush model in pigs withstandard fibrin stents as controls. After 24 hours, the stents werecompared for flow and were then examined histologically. While flow didnot differ in a statistically significant manner between the controlstent and the barium heparinate stent, the histological study showedsubstantially reduced clot formation on the barium heparinate stent(FIG. 5a) when compared with the control stent (FIG. 5b).

[0046] The complete disclosures of all patents, patent applications, andpublications referenced herein are incorporated herein by reference asif individually incorporated. Various modifications and alterations ofthis invention will become apparent to those skilled in the art withoutdeparting from the scope and spirit of this invention, and it should beunderstood that this invention is not to be unduly limited toillustrative embodiments set forth herein.

We claim:
 1. A system for use in the prevention or treatment of anarterial injury comprising: a drug eluting stent and a deliverycatheter, wherein said drug eluting stent comprises: a) a stentframework; and b) a porous material having a consistently distributedporosity with a plurality of particles of a water-insoluble salt of atherapeutic material dispersed throughout said porous material.
 2. Thesystem of claim 1, wherein said stent framework is a metallic material.3. The system of claim 1, wherein said stent framework is a polymericmaterial.
 4. The system of claim 1, wherein said stent framework isselected so as to allow said stent to be self-expanding.
 5. The systemof claim 1, wherein said stent framework is a combination of metallicand polymeric elements.
 6. The system of claim 3, wherein said polymericmaterial is nonbioadsorbable.
 7. The system of claim 3, wherein saidpolymeric material is bioadsorbable.
 8. The system of claim 3, whereinsaid polymeric material is a composite of bioadsorbable andnonbioadsorbable polymeric materials.
 9. The system of claim 1, whereinsaid stent framework is a composite of bioadsorbable andnonbioadsorbable elements.
 10. The system of claim 9, wherein saidbioadsorbable element is a polymeric material and said nonbioadsorbableelement is a metallic material.
 11. The system of claim 6, wherein saidnonbioadsorbable polymeric material is selected from the groupconsisting of polyethylene terephthalate, polyurethane urea andsilicone.
 12. The system of claim 8, wherein said nonbioadsorbablepolymeric material is selected from the group consisting of polyethyleneterephthalate, polyurethane urea and silicone.
 13. The system of claim1, wherein said porous material is a film disposed on the outer surfaceof said stent framework.
 14. The system of claim 13, wherein said filmis selected from the group consisting of TEFLON, silicone, polyurethane,polysulfone, polyethylene, polypropylene, polyamide, polyester,polytetrafluoroethylene, and a combination of two or more of thesematerials.
 15. The system of claim 13, wherein said film is selectedfrom the group consisting of a natural hydrogel, a synthetic hydrogel,and cellulose, and a combination of two or more of these materials. 16.The system of claim 1, wherein said porous material is incorporated intosaid stent framework.
 17. The system of claim 16, wherein said porousmaterial is selected from the group consisting of TEFLON, silicone,polyurethane, polysulfone, polyethylene, polypropylene, polyamide,polyester, polytetrafluoroethylene, and a combination of two or more ofthese materials.
 18. The system of claim 16, wherein said porousmaterial is selected from the group consisting of a natural hydrogel, asynthetic hydrogel, and cellulose, and a combination of two or more ofthese materials.
 19. The system of claim 1, wherein said water-insolublesalt of a therapeutic material comprises an antithrombotic material. 20.The system of claim 19, wherein said antithrombotic material is heparin.21. The system of claim 1, wherein said water-insoluble salt of saidtherapeutic material is selected from the group consisting of barium,and calcium salts of said therapeutic material.
 22. The system of claim1, wherein said therapeutic material comprises at least one substanceselected from the group consisting of an antithrombotic, an antiplateletagent, an anticoagulant agent, an antimitotic agent, an antioxidantagent, an antimetabolite agent, and an anti-inflammatory agent.
 23. Thesystem of claim 1, wherein said therapeutic material is effective totreat or prevent restenosis.
 24. The system of claim 1, wherein saidwater-insoluble salt of a therapeutic material is a radioactive salt.25. A system for use in the prevention or treatment of an arterialinjury comprising: a drug eluting stent and a delivery catheter, whereinsaid drug eluting stent comprises: a) a stent framework; and b) a porousmaterial having a consistently distributed porosity with a plurality ofparticles of a water-insoluble salt of a therapeutic material dispersedthroughout said porous material, wherein said stent framework is acomposite of at least one bioadsorbable polymeric material and at leastone nonbioadsorbable polymeric material.
 26. The system of claim 25,wherein said polymeric materials are selected so as to allow said stentto be self-expanding.
 27. The system of claim 25, wherein saidnonbioadsorbable polymeric material is selected from the groupconsisting of polyethylene terephthalate, polyurethane urea andsilicone.
 28. The system of claim 25, wherein said porous material is afilm disposed on the outer surface of said stent framework.
 29. Thesystem of claim 28, wherein said film is selected from the groupconsisting of TEFLON, silicone, polyurethane, polysulfone, polyethylene,polypropylene, polyamide, polyester, polytetrafluoroethylene, and acombination of two or more of these materials.
 30. The system of claim28, wherein said film is selected from the group consisting of a naturalhydrogel, a synthetic hydrogel, and cellulose, and a combination of twoor more of these materials.
 31. The system of claim 25, wherein saidporous material is incorporated into said stent framework.
 32. Thesystem of claim 31, wherein said porous material is selected from thegroup consisting of TEFLON, silicone, polyurethane, polysulfone,polyethylene, polypropylene, polyamide, polyester,polytetrafluoroethylene, and a combination of two or more of thesematerials.
 33. The system of claim 31, wherein said porous material isselected from the group consisting of a natural hydrogel, a synthetichydrogel, and cellulose, and a combination of two or more of thesematerials.
 34. The system of claim 25, wherein said water-insoluble saltof a therapeutic material comprises an antithrombotic material.
 35. Thesystem of claim 34, wherein said antithrombotic material is heparin. 36.The system of claim 25, wherein said water-insoluble salt of saidtherapeutic material is selected from the group consisting of barium,and calcium salts of said therapeutic material.
 37. The system of claim25, wherein said therapeutic material comprises at least one substanceselected from the group consisting of an antithrombotic, an antiplateletagent, an anticoagulant agent, an antimitotic agent, an antioxidantagent, an antimetabolite agent, and an anti-inflammatory agent.
 38. Thesystem of claim 25, wherein said therapeutic material is effective totreat or prevent restenosis.
 39. The system of claim 25, wherein saidwater-insoluble salt of a therapeutic material is a radioactive salt.